Migraine Prevalence, Environmental Risk, and Comorbidities in Men and Women Veterans

This cross-sectional study examines the prevalence of migraine, associated health comorbidities, and potential military service exposures among men and women veterans in the US.


Introduction
Migraine is a common and disabling disorder and a leading cause of neurological primary care visits. 1 Veterans face a unique challenge, as they have a higher prevalence of migraine and an increased risk for comorbidities, including traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), depression, and anxiety, compared with the general population, which can interact with migraine and worsen symptoms. 2,3While the underlying mechanisms of migraine may be similar in veterans and the general population, 4 the impact of military service and other health comorbidities can result in differences in the prevalence, presentation, and treatment of migraine. 1These differences, potentially tied to the physical and psychological stress of military service, are not fully understood.
Veterans may also face unique barriers to accessing appropriate treatment for migraine, 5 including difficulties accessing health care, the stigma associated with seeking care, and limited access to specialized headache clinics.Despite the significant impact of migraine on veterans, there has been limited systematic research 6 and a lack of understanding of the general epidemiological characterization of migraine in this population across several specific topics.

Prevalence
Migraine affects up to 12% to 15% of the general population. 7However, estimates of migraine prevalence in veterans range from 5% to 10% in general veteran samples 6,8,9 to 36% in veterans of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF). 10Although the causes underlying the high rate of migraine in veterans and varying prevalence rates across service eras [11][12][13] are not fully understood, various exposures, including TBI, concussion, combat, explosions, and accidents, have been considered possible contributory factors.For example, service during OEF/OIF has been associated with a high risk of TBI 13 with 485 553 TBIs reported by the US Department of Defense between 2000 and 2023, 14 which can result in persistent posttraumatic headache, usually presenting with migraine-like phenotype. 15,16Similarly, service during the Vietnam and Gulf War eras was associated with various chemical exposures (eg, Agent Orange, anti-nerve agent pills), also considered potential contributors to higher rates of migraine in these veteran cohorts. 17,18Evaluating the prevalence of migraine across the veteran population rather than isolated cohorts may elucidate factors affecting prevalence.

Gender Differences
Migraine is 2 to 3 times more prevalent and more burdensome 32,33 in women veterans than men veterans, [32][33][34] but research on women veteran health, including migraine, continues to lag. 35derstanding migraine comorbidities in men and women veterans is critical, as various health comorbidities associated with migraine have been linked with worse migraine phenotypes, 22 increased migraine severity, increased headache days per month, 23 and progression to chronic migraine. 36

The Present Study
We used a large epidemiological sample of men and women veterans in the Million Veteran Program (MVP) to address these research gaps.We aimed to (1) establish the lifetime prevalence of migraine in veterans of all eras; (2) characterize service history, environmental risk factors, and health comorbidities in those with and without migraine; and (3) examine the role of gender in these associations.By improving our understanding of migraine in this population, our goal is to inform more specialized, effective treatments for migraine and reduce the burden of this debilitating disorder.

Participants and Procedures
Data for this study were from the MVP, a national ongoing research project examining genetic traits, health habits, and environmental factors' impact on veteran health.The design and recruitment procedures of MVP have been documented previously. 37The MVP protocol was approved by the Veterans Affairs (VA) Central Institutional Review Board (cIRB) in 2010, and study enrollment began

Data Sources, Measures, and Analyses
Informed consent was obtained on the day of the MVP study visit, and veterans were asked to complete the self-report baseline survey, as detailed in Gaziano et al. 37 This survey gathered demographic data, such as race and ethnicity, health, lifestyle, military, medical, and family history.
The current study used data on overall health status and pain interference with work throughout the previous 4 weeks, pain level throughout the past week, smoking status, history of diagnosis, military service history, and environmental exposures during military service.
As part of the baseline survey, veterans indicated a history of diagnosis of 75 health conditions from various health domains, including psychiatric, neurologic, hearing and vision problems, infectious disease, respiratory, musculoskeletal, cardiac, and other health conditions.Migraine was assessed as part of self-reported diagnoses.We examined the association with migraine International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes (eTable 2 in Supplement 1) in the electronic health record (EHR) to determine the validity of self-reported migraine diagnosis.The tetrachoric correlation between self-reported migraine and lifetime ICD-9 and ICD-10 code diagnosis for migraine in the EHR was 0.79 (491 604; 95% CI, 0.79-0.79).
Prescription drug use and alcohol use were obtained from EHR data, part of the VA Corporate Data Warehouse (CDW). 38Further information on data types and measures is described in eMethods in Supplement 2).

Statistical Analysis
All analyses were conducted in R version 4.2.3 (R Project for Statistical Computing). 39Demographic data, health conditions, and environmental exposures in veterans with self-reported migraine were reported as mean (SD) or counts with percentages.Men and women were analyzed separately, and differences were assessed using t tests for means and 2 sample tests of proportions.To evaluate the presence of migraine across various environmental factors, ORs were adjusted for appropriate covariates, including age, gender, service era, and exposure.For example, odds ratios (ORs) adjusted for Agent Orange included age, gender, and Vietnam War.Because veterans could endorse multiple categories, models were fitted separately for each military branch, service era, and environmental exposure, directly comparing veterans with that experience with veterans without that experience.
Logistic regression models with ORs and 95% CIs were used to report the likelihood of association with health conditions for the overall sample (adjusted for age and gender) and across gender (adjusted for age).Further information on data analyses is described in the eMethods in Supplement 2.
The significance level was set at P <.001 to account for the large sample size.As described in the eMethods in Supplement 2, to control for type 1 error, false discovery rate (FDR) was used due to the study's large sample size and multiple tests.FDR significance values (q) are reported as P values in the health condition results.Data were analyzed from December 2022 to July 2023.

Demographic Characteristics and Health Habits
This study used data from 491 604 veterans (mean [SD] age, 65.1 [12.5]  those without, less likely to be married or cohabiting, had higher education levels, and less likely to report an annual household income less than $60 000. Veterans with migraine compared with veterans without migraine had a slightly higher body mass index (BMI, calculated as weight in kilograms divided by height in meters squared; mean [SD], 29.3 [5.9] vs 29.6 [5.6]; P < .001)and were more likely to report poor health (16.1% vs 8.9%; P < .001)and higher pain levels (mean [SD], 5.6 [2.6] vs mean [SD].3.9 [2.8]; P < .001).Additionally, 52.3% of veterans with migraine reported quite a bit or extreme pain interference at work compared with 28.1% of veterans without migraine (P < .001).Veterans with migraine were more likely to not smoke (35.3% vs 28.4%; P = <.001), had lower alcohol use, and had more antimigraine agent (36.3% vs 1.8%; P > .001)and lifetime opioid analgesics (76.4% vs 63.6%; P > .001)prescriptions.
Across men and women with migraine, the mean (SD) BMI was similar (men, 29.3 [5.7]; women, 28.8 [5.6]; P = .40),but smoking status varied with 49.2% of women reporting having never smoked compared with 35.3% of men (P < .001).Men had a higher former smoking rate than women (46.6% vs 30.9%;P < .001),while current smoking rates were similar.Women reported better health than men (54.5% vs 44.5%), and men reported more pain interference than women (53.6% vs 48.3%) (P < .001).Women had more antimigraine medication use than men (55.0%vs 30.1%;P < .001)and received slightly more total lifetime antimigraine prescriptions than men (23.1 prescriptions vs 22.9 prescriptions; P < .001).Opioid medication use was somewhat higher in women than in men (78.8% vs 75.6%;P < .001),but men received more total lifetime prescriptions compared with women (39.9 prescriptions vs 34.9 prescriptions; P < .001).Although some differences were small, nearly all variables showed significant differences across gender due to sample size (Table 1).

Military Service and Environmental Exposure
When controlling for gender and age within the total sample (

Self-Reported Health Conditions
eTable 1 in Supplement 1 provides the prevalence of health conditions in the overall sample and by migraine status and by migraine status and gender.Within the total sample, migraine was associated with most health conditions examined when adjusted for age and gender (Figure 2 and Figure 3).).Notably, while the associations were slightly weaker in women than men, the overall pattern remained consistent.

Among men (
Significant interactions between migraine and gender were present (with most associations stronger in men) for over half of the evaluated conditions (indicated by asterisks in eFigure 1 and eFigure 2 in Supplement 2), including all psychiatric disorders.

Discussion
We used data from the MVP to assess the lifetime prevalence of migraine among US veterans, considering gender, service eras, environmental risk factors, and health comorbidities.Lifetime migraine prevalence was 8.2% in men and 30.1% in women, with the highest rates among Hispanic or Latinx women and in more recent service eras.Veterans with migraine were more likely to report additional psychiatric, neurological, and digestive conditions.Importantly, our results showed higher migraine prevalence in the context of specific aspects of military service and environmental exposures.These findings shed light on the complex association between migraine, gender, and military service-related environmental exposures, particularly among the often-understudied demographic of women veterans.In deepening the insights of prior work, 6  elucidates the interplay between migraine, gender, diverse lifetime comorbidities, and various environmental exposures.
Our results aligned with previous research. 6The higher prevalence of migraine among women, especially Hispanic or Latinx women, supported earlier findings of increased burden of migraine in these populations. 40The higher prevalence of migraine in women than men echoes previous research and may be attributable to endocrine, genetic, and environmental influences. 41The increased prevalence of migraine in veterans, especially in more recent military service eras, supports the evolving interplay between contemporary service conditions and migraine incidence.
Additionally, our results support the significant comorbidity of migraine with psychiatric,  mandates comprehensive health evaluations for all veterans to identify and address potential environmental exposures and expands VA health care and benefits for veterans exposed to burn pits, Agent Orange, and other toxins.Such screening may help identify the factors contributing to migraine and other health conditions, ultimately enabling appropriate treatment.
The association between migraine and quality of was evident, as veterans with migraine reported diminished general health, increased pain levels, and interference with work.3][44] Interdisciplinary approaches to migraine management, encompassing pharmacological and nonpharmacological treatments, are crucial for addressing the diverse needs of impacted individuals. 45,46Because comorbid pain, neurological, psychiatric, and digestive disorders can affect the association between migraine, health characteristics including pain and opioid use, a multifaceted approach to migraine research to understand these complicated associations and to clinical management is essential.
Enhanced awareness and education for health care clinicians and the public can promote earlier detection of migraine symptoms, leading to better diagnoses and patient outcomes. 47These efforts can also mitigate the impact of migraine and associated comorbidities, contributing to more efficient health care use.To ensure effective treatment and prevention, specialized screening and interventions should be considered for specific groups, such as women and Hispanic or Latinx veterans.
Finally, the comorbidity of migraine with other health conditions, particularly psychiatric and neurological disorders, was consistent with previous work 22,24,[48][49][50][51] and highlights the importance of screening and addressing cognitive and mental health concerns in veterans with migraine rather than regarding migraine as an adverse effect of other conditions.In line with this, comprehensive neurological evaluations for veterans with migraine are essential, given the strong association with conditions like TBI.The higher prevalence of digestive system problems, such as IBS and others, in veterans with migraine warrants further investigation.

Limitations
This study has limitations.Using data from a single source (the MVP) may limit generalizability due to potential biases of the sample, including demographic and clinical characteristics.Diagnoses were based on self-report rather than the more rigorous International Classification of Headache Disorders 3rd edition criteria or a validated screener, which might lead to underdiagnosis.This self-report approach can introduce recall or social desirability bias, and recall can be influenced by an individual's health status, even though a strong correspondence with medical record data was observed.The cross-sectional design restricts establishing causality or directionality, necessitating longitudinal studies to elucidate temporal associations and potential causal pathways.Detailed clinical or diagnostic information on migraine was not available; therefore, future studies can replicate these findings with clinical samples using clinical and diagnostic information.

Conclusions
In this cross-sectional study of the association between migraine, environmental exposures, and various health conditions in US veterans, findings underscored the need for more research on migraine etiology, diagnosis, and management.Our results suggested that comprehensive and targeted migraine management strategies should be prioritized to address the unique needs of different veteran populations and at-risk groups.This work emphasized that collaborative efforts among health care clinicians, researchers, and policy makers within the VA health care system are essential to improve the diagnosis and treatment of migraine.
in 2011.The VA cIRB and the Research and Development Committee at VA San Diego Healthcare System approved the current analyses conducted in 2023.MVP veterans with demographic information and complete data on the baseline survey were included.From 819 417 enrolled veterans, 327 692 were excluded due to missing baseline survey data and 121 due to missing gender, resulting in an analytic sample of 491 604 (59.9%).We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

Figure 1 .
Figure 1.Migraine Prevalence in Men and Women Veterans Across Race or Ethnicity, Branch of Service, Service Era, Deployment, and Environmental Exposure

Figure 2 .
Figure 2. Self-Reported Neurological, Psychiatric, Digestive, and Circulatory Conditions Across Migraine Status for the Overall Sample

Table 1 .
Demographic and Health Characteristics of the Total Sample and by Gender and Self-Reported Migraine Diagnosis (continued) African American, 12.4%; Hispanic or Latino/a/x, 13.3%; White, 9.3%, and those reporting another race, 14.9%.
Abbreviations: AUDIT-C, Alcohol Use Disorders Identification Test-Concise; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); GED, general education diploma; NA, not applicable.a t Test for means or 2 sample tests of proportions.b Comparison between men with migraine and women with migraine.c Percentage with migraine: d Includes American Indian or Alaskan Native, Asian, Native Hawaiian or Pacific Islander, and all other races not listed.

Table 2 .
Associations Between Migraine and Military Service and Environmental Exposure for Total Sample and by Gender from May 1975 to July 1990 (AOR, 1.31; 95% CI, 1.28-1.33)hadhigherodds of migraine compared with veterans who did not serve during those eras.Among men (Table2), service in the US Army had slightly increased odds of migraine self-report (AOR, 1.09; 95% CI, 1.07-1.11),asdidservice in the August 1990 to August 2001 era, including the Gulf War (AOR, 1.39; 95% CI, 1.35-1.42),andthepost-Vietnam era from May 1975 to July 1990 (AOR, 1.30; 95% CI, 1.27-1.33).Among women (Table2), service in the US Air Force had slightly increased odds of migraine self-report (AOR, 1.10; 95% CI, a Adjusted for age and gender.bAdjustedforage.cPvalue for gender by environmental factor interaction.Significance value for the interaction between gender and environmental exposure factor, adjusted for age.dOther branch of service includes Coast Guard, National Guard, Merchant Marines, National Oceanic and Atmospheric Administration, Public Health Service.e Adjusted for age and Vietnam War.f Adjusted for age, service during the Gulf War, and service after September 2001.era Migraine Prevalence, Environmental Risk, and Comorbidities in Men and Women Veterans our research further JAMA Network Open | Neurology JAMA Network Open.2024;7(3):e242299.doi:10.1001/jamanetworkopen.2024.2299(Reprinted) March 14, 2024 9/16 Downloaded from jamanetwork.comby guest on 03/21/2024 , and digestive health issues, reinforcing the importance of integrated health care approaches in managing these comorbidities.We provide novel insights into the association between migraine and specific environmental exposures associated with military service.Our results suggest that certain occupational or environmental factors, such as Agent Orange and chemical and biological welfare, are associated with migraine in veterans.The increased prevalence of migraine suggests that such exposures may elevate the risk of associated conditions with potential gender-specific impacts.Men may exhibit greater vulnerability to certain service-related environmental triggers, either through genetic predisposition or environmental exposure.Our results the potential differential impact of these exposures on men and women, emphasizing the need for more gender-focused research and health care strategies to address these disparities.Recognizing the impact of environmental exposures, the VA's implementation of the Honoring Our Promise to Address Comprehensive Toxics (PACT) Act of 2022 environmental exposure screening law is timely and commendable.PACT neurological